PROJECT SUMMARY Protein interactions are primary determinants of function in living systems. Functional regulation can be achieved through changes in protein interactions resultant from mutations, altered protein abundance levels, posttranslational modifications, conformational changes or altered protein localization. The importance of the protein interaction network for understanding cellular function has long been primary motivation for its mapping. However, the concept of an ?edgotype? has more recently arisen to describe the protein interaction network where nodes are proteins, edges represent interactions and edge-level changes, or edgetic perturbations, define an edgotype resultant from genetic mutations. While genetic mutations are critical for stable phenotype definition, most drugs target proteins and alter one or more of the categories; abundance, modifications, conformation, or localization of target, downstream and off-target proteins. This project will focus efforts to extend the edgotype concept using a general mass spectrometry-based approach to visualize large-scale pharmacological effects on protein structures and interactions in cells to significantly advance cell- based pharmacological studies.